Tests for Non-Hodgkin Lymphoma in Children

Non-Hodgkin lymphoma (NHL) is usually found when a child is brought to a doctor because of signs or symptoms he or she is having. This might lead the doctor to suspect the child could have a lymphoma, but tests are needed to confirm this. The exams and tests below are used to diagnose lymphoma, to find out what type it is, and to learn how advanced it is.

Medical history and physical exam

If any signs and symptoms suggest a child might have lymphoma, the doctor will ask about the symptoms and how long they have been present. The doctor might also ask if there is any history of possible risk factors, such as immune system problems.

During the physical exam, the doctor will probably focus on any enlarged lymph nodes or other areas of concern. For example, the abdomen (belly) may be felt for signs of an enlarged spleen or liver.

The most common cause of enlarged lymph nodes in a child is an infection, so this is often what doctors think of first. Because of this, the diagnosis of NHL in a child can sometimes be delayed. There is usually little cause for concern in children with swollen lymph nodes unless they are very large (more than 1 inch across). Even in these instances, the child is usually watched closely for a time or given a course of antibiotics first to see if the nodes will shrink. If they don't, more tests are done, such as a biopsy to remove part or all of a swollen node (see next section). But if the lymph nodes seem to be growing quickly or the child’s health seems to be getting worse, a biopsy may be needed right away.

Biopsy

A doctor can’t diagnose NHL in a child based only on symptoms or a physical exam. Most of the symptoms NHL can cause are more often caused by other problems, like infections. They may also be caused by other kinds of cancers. If a child does have NHL, it’s important to know which type it is, because each type is treated slightly differently.

The only way to diagnose these things for sure is to remove some or all of an abnormal lymph node (or tumor) for viewing under a microscope and other lab tests. This is called a biopsy.

Types of biopsies used to diagnose non-Hodgkin lymphoma

There are several types of biopsies. Doctors choose which one to use based on the situation. The goal is to get a sample large enough to make an accurate diagnosis as quickly as possible, with as few side effects as possible.

Surgical (excisional or incisional) biopsy: These are the most common types of biopsies done if lymphoma is suspected. An exception might be large chest tumors, for which a needle biopsy (described below) might be used instead.

In these procedures, a surgeon cuts through the skin to remove either an entire lymph node (excisional biopsy) or a small part of a large tumor (incisional biopsy).

If the node is near the skin surface, this is an operation that might be done with either local anesthesia (numbing medicine at the biopsy site) and sedation, or with general anesthesia (where the child is in a deep sleep). If the node is inside the chest or abdomen, then general anesthesia is typically needed.

This method almost always provides enough of a sample to diagnose the exact type of NHL.

Needle biopsy: These biopsies use hollow needles to remove small pieces of tissue. There are 2 main types:

In an fine needle aspiration (FNA) biopsy, the doctoruses a very thin, hollow needle attached to a syringe to withdraw (aspirate) a small amount of tissue from an enlarged lymph node or a tumor mass.

For a core needle biopsy, the doctor uses a larger needle to remove a slightly larger piece of tissue.

If an enlarged lymph node is just below the skin, the doctor can aim the needle while feeling the node. If the enlarged node or tumor is deep in the body (such as in the chest or abdomen), the doctor can guide the needle while watching it on a CT scan or ultrasound (see discussion of imaging tests later in this section).

The main advantage of a needle biopsy is that it does not require surgery. This can be especially important for children with tumors in the chest, because general anesthesia (where the child is in a deep sleep) can sometimes be dangerous for these children. A needle biopsy is also useful when the lymphoma is in places other than the lymph nodes, such as the bones.

In children, needle biopsies can often be done using local anesthesia to numb the area, along with sedation to make the child sleepy. General anesthesia is needed less often.

The main drawback of needle biopsies (especially FNA) is that sometimes the needle might not remove enough of a sample to make a definite diagnosis. Most doctors don’t use needle biopsies if they strongly suspect lymphoma (unless other types of biopsies can’t be done for some reason). But if the doctor suspects that lymph node swelling is caused by an infection (even after antibiotics), a needle biopsy may be the first type of biopsy done. If a biopsy is needed, doctors typically prefer to do a core biopsy instead of FNA. An excisional biopsy might still be needed to diagnose and classify lymphoma, even after a needle biopsy has been done.

Once lymphoma has been diagnosed, needle biopsies are sometimes used to check areas in other parts of the body that might be lymphoma spreading or coming back after treatment.

Other types of biopsies

These other types of biopsies are not normally used to diagnose lymphoma, but they might be done if a lymphoma has already been diagnosed to help show how far it has spread.

Bone marrow aspiration and biopsy: These tests can show if a lymphoma has reached the bone marrow. The 2 tests are usually done at the same time. The biopsy samples are usually taken from the back of the pelvic (hip) bones, although sometimes they may be taken from the front of the hip bones or from other bones.

For a bone marrow aspiration, the skin over the hip and the surface of the bone is numbed with local anesthetic. In most cases, children will be given other medicines to make them drowsy or asleep during the biopsy. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is put into the bone. Once the biopsy is done, pressure will be applied to the site to help stop any bleeding.

Lumbar puncture (spinal tap): This test is used to look for lymphoma cells in the cerebrospinal fluid (CSF), which is the fluid that surrounds the brain and spinal cord.

For this test, the doctor first numbs an area in the lower part of the back near the spine. The doctor usually also gives the child medicine to make him or her sleep during the procedure. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.

In children already diagnosed with lymphoma, a lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of lymphoma to the spinal cord and brain.

Pleural or peritoneal fluid sampling: If lymphoma spreads to the thin membranes that line the inside of the chest and abdomen it can cause fluid to build up. Pleural fluid (inside the chest) or peritoneal fluid (inside the belly) can be removed by putting a hollow needle t through the skin into the chest or abdomen.

When this procedure is used to remove fluid from the chest, it’s called a thoracentesis.

When it's used to collect fluid from inside the belly, it’s known as a paracentesis.

Before the procedure, the doctor uses a local anesthetic to numb the skin and may give the child other medicines so they are drowsy or asleep during the procedure. The fluid is then drawn out and looked at with a microscope to check for lymphoma cells

Lab tests on biopsy samples

All biopsy samples and fluids are looked at by a pathologist (a doctor with special training in using lab tests to identify cancer cells). The doctor uses a microscope to look at the size and shape of the cells and how they are arranged. This can show if a child has lymphoma, and sometimes what type of lymphoma it is, as well. But usually other types of lab tests will be needed, too.

Flow cytometry and immunohistochemistry

For flow cytometry and immunohistochemistry, samples of cells are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For immunohistochemistry, the cells are then looked at with a microscope to see if the antibodies stuck to them (meaning they have these proteins), while for flow cytometry a special machine is used.

These tests can help determine if a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. The tests can also be used for immunophenotyping – determining which type of lymphoma a child has, based on certain proteins in or on the cells. Different types of lymphocytes have different proteins on their surface, which correspond to the type of lymphocyte and how mature it is.

Chromosome tests

Doctors use these tests to evaluate the chromosomes (long strands of DNA) in the lymphoma cells. In some types of lymphoma, the cells have changes in their chromosomes, such as having too many, too few, or abnormal chromosomes. These changes can often help identify the type of lymphoma.

Cytogenetics: In this type of lab test, the cells are looked at under a microscope to see if the chromosomes have any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the lymphoma cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be seen with a microscope.

Fluorescent in situ hybridization (FISH): This test looks more closely at lymphoma cell DNA using fluorescent dyes that only attach to specific gene or chromosome changes. FISH can find most chromosome changes (such as translocations) that can be seen under a microscope on standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing. FISH is very accurate and results are usually ready within a couple of days, which is why this test is now used in many medical centers.

Polymerase chain reaction (PCR): This is a very sensitive DNA test that can also find some chromosome changes too small to be seen with a microscope, even if there are very few lymphoma cells in a sample.

Blood tests

Blood tests measure the amounts of certain types of cells and chemicals in the blood. They are not used to diagnose lymphoma, but they might be one of the first types of tests done in children with symptoms to help the doctor determine what is going on. If a child has been diagnosed with lymphoma, these tests can also sometimes help tell how advanced the lymphoma is.

The complete blood count (CBC) is a test that measures the levels of different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. In children already known to have lymphoma, low blood cell counts might mean that the lymphoma is growing in the bone marrow and damaging new blood cell production.

Blood levels of lactate dehydrogenase (LDH) may be checked. LDH will often be abnormally high in patients with fast-growing lymphomas.

Blood chemistry tests can help detect liver or kidney problems caused by the spread of lymphoma cells or certain chemotherapy drugs. These tests can also help determine if treatment is needed to correct low or high blood levels of certain minerals.

Tests may also be done to make sure the blood is clotting properly.

For some types of lymphoma, the doctor might also want to order other blood tests to see if the child has been infected with certain viruses, such as the Epstein-Barr virus (EBV), hepatitis B virus (HBV), or human immunodeficiency virus (HIV). Infections with some of these viruses can affect your child’s treatment.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive substances to create pictures of the inside of the body. These tests might be done for a number of reasons, including:

To look for possible causes of certain symptoms (such as trouble breathing)

A child with a known or suspected lymphoma might need one or more of these tests.

Chest x-ray

A chest x-ray may be done to look for enlarged lymph nodes inside the chest.

Computed tomography (CT or CAT) scan

The CT scan combines many x-rays to make detailed, cross-sectional images of the body. CT scans can be used to look for enlarged lymph nodes or other masses in the chest, abdomen, pelvis, head, and neck.

During the test, your child will need to lie still on a table that slides in and out of the ring-shaped scanner. Some younger children may be given medicine to help keep them calm or even asleep during the test to help make sure the pictures come out well.

CT-guided needle biopsy: A CT scan can also be used to guide a biopsy needle precisely into a suspected tumor or enlarged lymph node. For this procedure, the child remains asleep on the CT scanning table, while the doctor advances a biopsy needle through the skin and toward the area. CT scans are repeated until the needle is in the right place. A biopsy sample is then removed and looked at under a microscope.

Ultrasound (sonogram)

Ultrasound uses sound waves and their echoes to create pictures of internal organs or masses.

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside the abdomen (belly) for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. (It can’t be used to look inside the chest because the ribs block the sound waves.) It is also sometimes used to help guide a biopsy needle into an enlarged lymph node.

Magnetic resonance imaging (MRI) scan

An MRI scan, like a CT scan, shows detailed images of soft tissues in the body. This test is not used as often as CT scans for lymphoma, but MRI is very useful for looking at the brain and spinal cord if a child has symptoms that might be caused by problems in the nervous system.

MRI scans take longer than CT scans, often up to an hour. Your child may have to lie inside a narrow tube, which can be distressing, so sedation is sometimes needed. Newer, more open MRI machines may be another option, although your child will still have to lie still.

Positron emission tomography (PET) scan

For a PET scan, a slightly radioactive sugar is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body within a day or so.) Because lymphoma cells grow quickly, they absorb more of the sugar. After about an hour, your child will be moved onto a table in the PET scanner. He or she will lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. Younger children may be given medicine to help keep them calm or even asleep during the test.

The picture from a PET scan is not detailed like a CT or MRI scan, but it provides helpful information about the whole body.

PET scans can be used for many reasons in a child with lymphoma:

They can help tell if an enlarged lymph node contains lymphoma.

They can help spot small areas in the body that might be lymphoma, even if the area looks normal on a CT scan.

They can help tell if a lymphoma is responding to treatment. Some doctors will repeat the PET scan after 1 or 2 courses of chemotherapy. If the chemotherapy is working, the lymphoma will no longer show up as well on the scan.

They can be used after treatment to help decide if an enlarged lymph node still contains lymphoma or is just scar tissue.

PET/CT or PET/MRI
scan: Some newer machines can do both a PET as well as a CT or MRI scan at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT or MRI scan.

Bone scan

A bone scan is not usually needed unless a child is having bone pain or has lab test results that suggest the lymphoma might have reached the bones.

For this test, a radioactive substance called technetium is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body within a day or so. Technetium travels to damaged areas of the bone over a couple of hours. Your child then lies on a table for about 30 minutes while a special camera detects the radioactivity and creates a picture of the skeleton. Younger children may be given medicine to help keep them calm or even asleep during the test.

A bone scan can detect bone damage from lymphoma. But a bone scan may also show other things that are not cancer, so other tests might be needed to be sure.